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Figure 6 | Journal of Translational Medicine

Figure 6

From: Programmed cell death-1 (PD-1) at the heart of heterologous prime-boost vaccines and regulation of CD8+ T cell immunity

Figure 6

Another dimension to the immune regulation of CD8+ T cells based on PD-1 expression. The lack of PD-1 up-regulation during priming may define a separate differentiation lineage. A current model (left side) depicts activation and differentiation of T cells, in relation to PD-1 expression, as a sequential upregulation and downregulation of PD-1, respectively. In this model, activated T cells unavoidably go through a stage in which they are sensitive to PD-1/PD-1L dependent negative regulatory mechanisms. Conversely, in the model depicted on the right side, the acquisition of PD-1 during T cell priming could be limited - depending on the priming regimen - thus yielding T cells that are not as susceptible to negative regulatory mechanisms associated with continuous or repeated antigen exposure. Thus, based on this model - and supported by recent evidence (42, 48) - immediate boosting would yield substantially higher immunity as opposed to immune 'exhaustion'. This enables the development of shortened immunization regimens utilizing a heterologous prime-boost strategy.

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